In the mid-1990s, the interest in adipose tissue was revived by the discovery of leptin. Since then numerous other hormones have been isolated from white adipose tissue that has no longer considered an inert tissue mainly devoted to energy storage but emerged as an active participant in regulating physiologic and pathologic processes, including immunity and inflammation. Adipose tissue produces and releases a variety of proinflammatory and anti-inflammatory factors, including the adipokines, as well as cytokines and chemokines. ⋯ In contrast, reduced leptin levels might predispose to increased susceptibility to infection caused by reduced T-cell responses in malnourished individuals. Altered adipokine levels have been observed in a variety of inflammatory conditions, although their pathogenic role has not been completely clarified. In this paper we want to review: (i) the role of adipose tissue in different biological processes, (ii) the functional and structural description of all the known adipokines subdivided in different subfamilies, (iii) the adipokine involvement in obesity and cancers, and (iv) the adipokine interactome.